Beta-arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways.
Recent advances in understanding beta-catenin-independent WNT (non-canonical) signalling suggest an increasing complexity, raising the question of how individual non-canonical pathways are induced and regulated. Here, we examine whether intracellular signalling components such as beta-arrestin (beta-arr) and casein kinases 1 and 2 (CK1 and CK2) can contribute to determining signalling specificity in beta-catenin-independent WNT signalling to the small GTPase RAC-1. Our findings indicate that beta-arr is sufficient and required for WNT/RAC-1 signalling, and that casein kinases act as a switch that prevents the activation of RAC-1 and promotes other non-canonical WNT pathways through the phosphorylation of dishevelled (DVL, xDSH in Xenopus). Thus, our results indicate that the balance between beta-arr and CK1/2 determines whether WNT/RAC-1 or other non-canonical WNT pathways are activated.
Bryja
Vítĕzslav
V
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Scheeles v ag 1, S-171 77 Stockholm, Sweden.
Schambony
Alexandra
A
Cajánek
Lukás
L
Dominguez
Isabel
I
Arenas
Ernest
E
Schulte
Gunnar
G
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D047389:Casein Kinase I / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D054262:Gastrulation; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D000071557:beta-Arrestins; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D019390:Arrestins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D000071557:beta-Arrestins; D047389:Casein Kinase I; D047390:Casein Kinase II; D020830:rac1 GTP-Binding Protein